This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Development of an effective HIV vaccine is the long term solution to control HIV/AIDS world wide and there is a need for the development of novel adjuvants to enhance the immunogenicity and efficacy of HIV vaccines. In this HIVRAD, we will use molecules that target mTOR (mammalian target of rapamycin) and CD40 pathways as novel adjuvants to elicit high levels of polyfunctional virus-specific CD8 T cells, CD4 T cells that are resistant to HIV infection and high avidity protective antibody, that will lead to enhanced control of HIV infection. This PPG has two projects and two cores. Our project 1 will test the potential of CD40L expressed on the surface of virus-like particles as an adjuvant to enhance the immunogenicity and efficacy of DNA/MVA SIV vaccine. Our project 2 will test the safety, immunogenicity and efficacy of rapamycin (inhibitor of mTOR) as an adjuvant for DNA/MVA SIV vaccine. In addition, we will test for the effects of rapamycin on other replication defective and replication competent viral vectors. Finally, we will test the synergy between inhibiting mTOR and activating CD40 pathways for enhancing the immunogenicity and efficacy of DNA/MVA SIV vaccines. The macaques studies that will be conducted in projects 1 and 2 will be supported by a non-human primate core. An administrative core will provide coordination between projects 1 and 2, and core B, and help with data management and data analyses. We just started these experiments.